1. Field of the Invention
The present invention relates to an improved method of making a therapeutic composition, Product R.sup.1, as hereinafter defined, which contains peptides and nucleotides. The components of Product R have molecular weights not more than 14 kilodaltons (KDa).
 FNT Product R was used as synonyms of RETICULOSE in some literature. For the purpose of the present application, Product R and RETICULOSE represent two distinct products.
2 . Description of the Related Art
The concept of an antiviral agent composed of peptones, peptides, proteins and nucleic acid was originated in 1934. After some years of experimentation, such an antiviral agent was modified by using bovine serum albumin in combination with peptone, and ribonucleic acid to produce an antiviral biotic agent which is nontoxic, free from anaphylactogenic properties and is miscible with tissue fluids and blood sera. The agent used to be described as a "lipopeptide-nucleic acid compound".sup.2 and registered under trademark RETICULOSE.RTM. by Chemico Laboratories, Inc. Physician Desk Reference, p 651, 1960. RETICULOSE.RTM. was reported as an antiviral agent for treating a variety of human viral infections, such as influenza, herpes, hepatitis A and B. It was then assumed that RETICULOSE.RTM. acts as an antiviral agent at least by increasing leukogenesis, synthesis of antibodies and enhancing phagocytosis. RETICULOSE.RTM. was last sold in the United States in 1964.
The method of making RETICULOSE.RTM. had been kept as a trade secret by the manufacture until the issuance of U.S. Pat. No. 5,849,196, which discloses the method of making RETICULOSE.RTM..
As disclosed in U.S. Pat. No. 5,849,196, the starting materials for making RETICULOSE.RTM. consist of, by weight, 40-50% of casein, 1-10% of blood albumin, 15-40% of beef peptone, 10-25% of RNA and 5-25% of sodium hydroxide. These starting materials are suspended in water which yields a ratio of proteins (casein, peptone and blood albumin) to water equals to about 4.3 to about 100 by weight. After an autoclaving treatment of the mixture of the starting materials, the resulting solution is filtered and pH is adjusted to approximately 8.5 and then to 7.8, after which the neutralized solution is filtered again. The pH is further adjusted to approximately 7.5 after the solution is diluted. Such process yields a mixture of peptides and nucleic acids having molecular weights in a range of approximately 1 to 25 KDa.
As taught by U.S. Pat. No. 5,849,196, the components over 15 KDa of the conventional composition of RETICULOSE.RTM. are more effective in treating viral diseases such as HIV, influenza virus, herpes simplex virus, etc. while the components in a range of approximately 1 to 15 KDa function as phagocytosis inhibitors.
However, the conventional methods suffers from several disadvantages: 1) the method does not ensure that each preparation produces the finished components having the same ratio, thereby the product is not reproducible; 2) the conventional method produces a wide range of the finished components, which makes the quality control of the preparation extremely difficult, if possible, because too many parameters need to be determined; 3) the presence of the higher molecular weight components, such as 25 KDa component, essentially peptides, increases the risk of hypersensitivity or immune reaction and renders the product less stable.
Therefore, it is desirable to have a product devoid of the deficiencies of conventional RETICULOSE.RTM. while maintaining its therapeutic properties.